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Epithelium Derived Rclaxing Factor-Its Role in Airway Hyperreactivity-

上皮源性松弛因子-其在气道高反应性中的作用-

基本信息

批准号：
01570419
负责人：
MUNAKATA Mitsuru
金额：
$ 1.34万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

It is speculated that airway epithelium regulate airway tone by releasing epithelium derived relaxing factor (EpDRF). To examine this possibility, we tried to answer the following questions.1. Does EpDRF really exist? : By applying co-axial bioassay system developed by Ilhan and Sahin, we confirmed that guinea-pig airway epithelium releases smooth muscle relaxant factor. There was a criticism that the relaxation seen in this system is caused by tissue hypoxia due to the narrowing of tracheal lumen. We modified co-axial bioassay system to eliminate reduction of tracheal diameter by inserting steel coil inside. With this system, we observed relaxation of rabbit aortic strip when the epithelium intact trachea was stimulated with acetylcholine. From these results we concluded that relaxation seen in this system is not due to tissue hypoxia but due to the release of relaxing factor from tracheal epithelium. In addition, we examined effects of atropine, pirenzepine, and 4-DAMP on acetylcholi … More ne induced EpDRF release. Atropine and 4-DAMP were about 50 times more potent in suppressing relaxation than pirenzepine. From these results, we concluded that epithelial muscarinic-M3 receptor stimulation may be responsiblc in inducing the release of EpDRF.2. What is EpDRF? : We examined the possibility that nitric oxide is one of EpDRF in guinea-pig airways. We studied first, whether nitric oxide could relax isolated tracheal strips, and then examined the effects of known inhibitors of endothelium-dependent relaxation (EDR) in the vascular system, hemoglobin methylene blue, and N^G-monomethyl-L-arginine (L-NMMA), on epithelium-dependent relaxation (EpDR) induced by hyperosmotic stimuli in perfused whole tracheal preparations, Nitric oxide produced concentration-dependent and complete relaxation of epithelium-denuded tracheal strips. Preincubation of the whole trachea with hemoglobin significantly inhibited osmotic-induced EpDR, but preincubation with methylene blue and L-NMMA did not. Hemoglobin introduced into the epithelial side after EpDR induced by hyperosmotic stimuli reversed relaxation, but methylene blue and L-NMMA did not. These results suggest that although EpDR and vascular EDR have some pharmacological similarities and nitric oxide can relax airway smooth muscle, nitric oxide is not responsible for osmotic-induced EpDR. Less

推测气道上皮通过释放上皮源性舒张因子（EpDRF）调节气道张力。为了检验这种可能性，我们试图回答以下问题。1. EpDRF真的存在吗？应用Ilhan和Sahin开发的同轴生物测定系统，我们证实了豚鼠气道上皮释放平滑肌松弛因子。有批评认为，该系统中观察到的松弛是由于气管腔变窄引起的组织缺氧引起的。我们改进了同轴生物测定系统，以消除插入钢丝圈内的气管直径减小。用该系统观察了乙酰胆碱刺激兔气管上皮时主动脉条的舒张反应。从这些结果中，我们得出结论，在这个系统中看到的松弛不是由于组织缺氧，而是由于气管上皮释放松弛因子。此外，我们还检测了阿托品、哌仑西平和4-DAMP对乙酰胆碱的影响。 ...更多信息 ne诱导EpDRF释放。阿托品和4-DAMP在抑制松弛方面比哌仑西平强约50倍。从这些结果中，我们得出结论，上皮毒蕈碱M3受体刺激可能在诱导EpDRF的释放中起作用。什么是EpDRF？我们研究了一氧化氮是豚鼠气道中EpDRF的可能性。我们首先研究了一氧化氮是否能舒张离体气管条，然后检测了血管系统中已知的内皮依赖性舒张（EDR）抑制剂血红蛋白亚甲蓝和N^G-单甲基-L-精氨酸（L-NMMA）对灌注的整个气管制备物中由高渗刺激诱导的上皮依赖性舒张（EpDR）的影响，一氧化氮产生浓度依赖性和完全松弛上皮剥脱气管条。用血红蛋白预孵育整个气管可显著抑制血小板诱导的EpDR，但用亚甲蓝和L-NMMA预孵育则无此作用。高渗刺激诱导EpDR后，血红蛋白进入上皮侧逆转松弛，但亚甲蓝和L-NMMA没有。这些结果表明，虽然EpDR和血管EDR有一些药理学上的相似之处，一氧化氮可以放松气道平滑肌，一氧化氮是不负责过敏性诱导的EpDR。少